Background and Aims. Previous studies have revealed the close relation of irisin with the occurrence and development of nonalcoholic fatty liver disease (NAFLD). A systematic review and meta-analysis were conducted to evaluate the association of circulating irisin levels and NAFLD. Methods. A systematic literature search of PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WANFANG, CNKI, and CBM databases was performed for relevant articles till August 2020. The weighted mean difference (WMD) values and 95% confidence intervals (CIs) were estimated to compare the case-control studies and pooled results using meta-analysis. Results. The meta-analysis included 5 case-control studies with a total of 1087 people. The results revealed that the circulating irisin levels showed no significant difference between NAFLD and healthy groups ( WMD = 7.51 (-12.53, 27.56) ng/ml, P > 0.05 ). Subgroup analysis based on races showed that the average irisin levels were higher in the NAFLD group than in the healthy group ( WMD = 13.53 (0.71, 26.34) ng/ml, P < 0.05 ) in 4 Asian studies. Subgroup analysis based on disease severity from 3 Asian studies revealed that the average irisin levels were higher in the NAFLD group than in the healthy group ( WMD = 25.1 (22.85, 27.51) ng/ml, P < 0.05 and WMD = 13.52 (22.85, 27.51) ng/ml, P < 0.05 , respectively). Subgroup analysis including 3 studies from Asia suggested that the irisin levels were higher in mild NAFLD than in moderate-severe NAFLD ( WMD = 11.68 (9.03, 14.32) ng/ml, P < 0.05 ). Conclusion. The average irisin levels might be higher in the NAFLD group than in the healthy group in Asians. The irisin levels in the mild NAFLD group might be higher than those in the moderate-severe group in Asians. It is important to monitor the changing trend of irisin levels in predicting the course of NAFLD disease and its changes.

Background Angiopoietin-like proteins (ANGPTLs) are closely related to insulin resistance and lipid metabolism, and may be a key in metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) (newly named metabolic-associated fatty liver disease (MAFLD)) is based on metabolic dysfunction. There may be some correlation between ANGPTLs and MAFLD, but the specific correlation is unclear. This study aims to explore the predictive role of ANGPTLs in MAFLD and its progression. Methods Seven databases (PubMed, EMBASE, Cochrane Library, CNKI, WANFANG, CBM and Clinicaltrials.gov) were searched with free terms and MeSH terms. The random-effects model was used to pool the data, and Standardized Mean Difference (SMD) and 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the article selection. RevMan 5.3, Stata 16 and MetaXL software were applied to analyse the data and the GRADE system was utilized to assess the certainty of evidence. Results After reviewing 823 related articles, 13 studies (854 cases and 610 controls) met the inclusion criteria, and contributed to this meta-analysis. The results showed that circulating ANGPTL8 level was significantly elevated in the MAFLD group than in the healthy control group (SMD = 0.97 pg/mL, 95%CI: 0.77, 1.18). Conversely, there was no significant difference in the ANGPTL4 (SMD = 0.11 ng/mL, 95%CI: − 0.32, 0.54) and ANGPTL3 (SMD = − 0.95 ng/mL, 95%CI: − 4.38, 2.48) between the two groups. Subgroup analysis showed that: 1) the MAFLD group had significantly higher ANGPTL8 levels than the healthy control group in Asian and other races; 2) the ANGPTL8 levels in Body Mass Index (BMI) > 25 kg/m2 patients with MAFLD were higher than those in the healthy control group; 3) the higher ANGPTL8 levels were observed in moderate to severe MAFLD group than the healthy control group. Meta-regression demonstrated that BMI might effectively explain the high heterogeneity. No significant publication bias existed (P > 0.05). The certainty of evidence was assessed as very low by the GRADE system. Conclusions The ANGPTLs may be related to MAFLD. The increased ANGPTL8 level may be positively correlated with different situations of MAFLD, which may act as a potential indicator to monitor the development trends.

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Introduction Pentraxin 3 (PTX3) is involved in inflammation regulation and has a certain association with infectious diseases. However, its specific correlation with infectious diseases remains controversial. This study aimed to analyze the association between them and explore the possible role of PTX3 in the prognosis of coronavirus disease 2019 (COVID-19). Methods Five databases (PubMed, Cochrane Library, Embase, Clinicaltrials.gov, and gray literature) were searched. Outcomes were expressed as a standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of included articles. Stata 12 and Meta-DiSc were applied to analyze the pooled data. Receiver operating characteristic (ROC) curves were conducted to determine the prognostic value of PTX3 for mortality. Results Six articles met the inclusion criteria. Circulating PTX3 levels had a nonsignificant difference between intensive care unit (ICU) and non-ICU patients with COVID-19 [SMD 1.37 (−0.08, 2.81); I 2 = 93.9%, P < 0.01], while the PTX3 levels in nonsurvival COVID-19 patients was significantly lower than those in survival patients [SMD −1.41 (−1.92, −0.91); I 2 = 66.4%, P = 0.051]. Circulating PTX3 had good mortality prediction ability (area under ROC curve, AUC = 0.829) in COVID-19. Funnel plots and Egger’s tests showed low probabilities of publication bias. Through sensitivity analysis, the results of this study were robust. Conclusion This study found that PTX3 was differentially expressed between survival and nonsurvival patients with COVID-19, while there was no significant difference between ICU and non-ICU patients. Meanwhile, circulating PTX3 may be a good biomarker for monitoring the prognosis of COVID-19, which may provide new ideas and directions for clinical and scientific research. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00730-9.

This study explored circulating pneumoproteins in the diagnosis, severity, and prognosis of COVID-19 by meta-analysis. We searched six English databases until December 16, 2021. Standardised mean difference (SMD) and 95% confidence interval (CI) were the overall outcomes. RevMan 5.3, Stata 16, and Meta-DiSc 1.4 were utilised for pooled analyses. Totally, 2902 subjects from 29 studies were included. COVID-19 patients had higher circulating KL-6, SP-D, and SP-A levels (SMD=1.34, 95% CI [0.60, 2.08]; SMD=1.74, 95% CI [0.64, 2.84]; SMD=3.42, 95% CI [1.31, 5.53], respectively) than healthy individuals. Circulating KL-6 levels were lower in survivors than in non-survivors (SMD=-1.09, 95% CI [-1.63, -0.55]). Circulating KL-6, SP-D, and RAGEs levels in mild to moderate patients were significantly lower (SMD=-0.93, 95% CI [-1.22, -0.65]; SMD=-1.67, 95% CI [-2.82, -0.52]; SMD=-1.17, 95% CI [-2.06, -0.28], respectively) than severe patients. Subgroup analysis and meta-regression suggested that age may be responsible for the heterogeneity (P=0.071) when analysing KL-6 in mild to moderate vs. severe patients. The meta-analysis of diagnostic accuracy including KL-6 for severity and mortality, and SP-D for severity demonstrated that they all had limited diagnostic values. Therefore, circulating pneumoproteins (KL-6, SP-D, and RAGEs) may reflect the diagnosis, severity, and prognosis of COVID-19 to some extent.